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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From May 11 to 26, 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Well conducted and well described study in accordance with GLP and OECD guideline 423 without any deviation.
Cross-reference
Reason / purpose:
read-across: supporting information

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Test material form:
liquid
Details on test material:
Batch No.: ED50F50R
Purity: 69% (sum of the three main constituents)
Name of test material (as cited in study report): Dipentene multiconstituent
Physical state: colourless liquid
Storage conditions: +2°C to +8°C, under nitrogen and protected from light

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle-France)
- Age at study initiation: 9 weeks
- Weight at study initiation: 207-230 g
- Fasting period before study: 24 hours
- Housing: In group of three animals in solid bottomed clear polycarbonate cages with sawdust bedding
- Diet: M20-SDS; ad libitum
- Water: Tap-water from public distribution system; ad libitum
- Acclimation period: Five days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 ° C
- Humidity: 30-70%
- Air change: 15 changes/hour
- Photoperiod: 12 hours dark/12 hours light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.28 mL/kg bw


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Dose was selected as per specified in the guidelines
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Six females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed every day, weighed on Day 0, 2, 7 and 14
- Necropsy of survivors performed: yes; animals were anaesthetised with sodium phenobarbital on Day 14 for necropsy
- Other examinations performed: Clinical signs
Statistics:
No data

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
1/6 on Day 6
Clinical signs:
- Decrease in spontaneous activity (4/6), muscle tone and righting reflex (3/6); increased salivation and piloerection (3/6) on Day 1; animals recovered to normal at 24 hours post dose.
Body weight:
- 7% decrease in body weight on Day 2 of animal that died on Day 6
- Absence of body weight gain on Day 2, recovered a normal body weight on Day 7
Gross pathology:
- White thinning of the corpus of the animal that died on Day 6
- Thickness (5/5) and white coloration (2/5) of forestomach
Other findings:
None

Any other information on results incl. tables

Table 1: Body weight and weight gain in grams

Animals

Day 0

Day 2

Day 2-Day 0

Day 7

Day 7-Day 0

Day 14

Day 14-Day 0

1

213

198

-15

Dead

Dead

Dead

Dead

2

230

237

7

256

26

285

55

3

207

211

4

245

38

249

42

4

219

225

6

241

22

264

45

5

221

222

1

252

31

268

47

6

225

239

14

263

38

272

47

Mean

219.2

222

2.8

251.4

31

267.2

47.2

Standard deviation

8.3

15.6

9.7

8.7

7.1

13

4.8

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 for dipentene was found to be greater than 2000 mg/kg bw in the Sprague-Dawley rats and therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.
Executive summary:

In an oral acute toxicity (limit test) study performed in accordance with GLP and OECD guideline 423, groups of six Sprague-Dawley female rats received a single oral (gavage) dose of dipentene at 2000 mg/kg bw. Animals were then observed for mortality, body weight and clinical signs of toxicity for 14 days and were all macroscopically necropsied after sacrifice. The observations were compared to historical control data.

One animal died on Day 6 during the study. A decrease in spontaneous activity (4/6), muscle tone and righting reflex (3/6) and increased salivation and piloerection (3/6) was noted on first day of study. All animals recovered to normal behavior at 24 hours post dose. A 7% decrease in body weight on Day 2 was observed in animal that died on Day 6. In surviving animals absence of body weight gain was noted on Day 2 that recovered normal body weight on Day 7. Thickness (5/5) and white coloration (2/5) of forestomach of surviving animals and white thinning of the corpus of the dead animal was noted on necropsy. The oral LD50 was found to be greater than 2000 mg/kg bw in rats.

The oral LD50 for dipentene was found to be greater than 2000 mg/kg bw in the Sprague-Dawley rats and therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.